Meningitis: Outbreak Large, Attack Rate Low

Action Points

The attack rate in the continuing meningitis outbreak is relatively low, with fewer than five exposed people in 20 having developed the disease.

Point out that there was marked variation among the states, from a high of 11.5 cases per 100 exposed patients in Michigan to a low of 0.1 in Pennsylvania.

The attack rate in the continuing meningitis outbreak is relatively low, with fewer than five exposed people in 20 having developed the disease, researchers reported.

Despite that and some variation in clinical presentation, it's "one of the largest outbreaks of healthcare–associated fungal meningitis reported to date" in the U.S., according to Rachel Smith, MD, of the CDC in Atlanta, and colleagues.

Smith and colleagues paint a picture of "substantial morbidity and mortality" mitigated by a rapid public health response that alerted physicians and patients to the evolving threat, in a preliminary report on the outbreak appearing online in the New England Journal of Medicine.

Indeed, the NEJM paper is "a snapshot of something that's still happening" and it's too early to make many definitive statements about the outbreak, Smith told MedPage Today.

Nonetheless, one key implication is that "it is imperative that steps are taken" to make sure that compounded medications labeled as sterile actually are sterile, she and colleagues concluded.

That's because the outbreak – with 620 cases and 39 deaths as of Dec. 17 -- has been linked to an injectable steroid, preservative-free methylprednisolone acetate, made by the New England Compounding Center in Framingham, Mass.

Three lots of the steroid were involved with some 17,675 vials distributed to 76 healthcare facilities in 23 states. Several unopened vials were later shown to be contaminated with a fungus, Exserohilum rostratum, that was also found in some patients.

The drug, given as epidural, spinal, paraspinal, or peripheral joint injections, was used to control chronic pain. All told, 13,534 people had been exposed to the tainted steroid, Smith and colleagues estimated.

As of Dec. 10, which was the cutoff date for the data in the analysis, there were 590 cases in 19 states, for an overall attack rate of 4.4 per 100 exposed people, they reported.

On the other hand, there was marked variation among the states, from a high of 11.5 cases per 100 exposed patients in Michigan to a low of 0.1 in Pennsylvania.

The differences are not likely to arise from variation in case finding, Smith said, because 99% of all exposed people have been contacted at least once. "We don't think this is detection bias," she added.

Instead, the researchers suggested such things as the level of contamination, the times the lots were received, length of storage, and injection practices might have played a role.

"We're still trying to figure out why some people didn't get sick and others did," Smith said.

In addition, the attack rates are likely to be underestimates because some cases have not yet had enough to time to become evident.

In a similar outbreak in 2002, the longest time from exposure to symptoms was 116 days, or nearly 4 months, the researchers noted. The tainted drugs in this outbreak were recalled Sept. 26; if the earlier pattern is repeated, new cases might be expected until late in January.

"We're certainly still concerned about the exposed patients," Smith said.

While the outbreak has been labeled as involving fungal meningitis, some patients have had other complaints and the pattern has been changing slightly over time, Smith said.

The agency had complete case data for 386 patients as of Nov. 26, the researchers reported and, of those, 300 had meningitis. But 65 had spinal or paraspinal infections, 10 had septic arthritis after a peripheral-joint injection, and five had stroke due to presumed meningitis.

In recent weeks, Smith said, doctors have been seeing more spinal and paraspinal infections, and fewer cases of meningitis. Indeed, in the first 2 weeks of December, CDC data show just four new cases of meningitis and 65 new spinal or paraspinal infections.

Outbreaks of fungal disease are relatively rare and this one began with a mystery, Smith noted.

It came to light Sept. 18 when clinicians in Nashville told the state health department they had a case of meningitis apparently associated with the fungus Aspergillus fumigatus.

The 56-year-old man, who later died, had been given spinal steroid injections at a local clinic.

Medical detective work by the state health department and the CDC found seven more cases in the next few days but, Smith said, "we had no idea what was causing this."

"All we knew was that (the new cases) had the same symptom profile, that they were very sick, and that some of them were having strokes," she said.

As well, they knew that all of the patients had been given injections of the steroid at the same clinic.

Traditional diagnostic tools were of little help because fungi are notoriously hard to pin down. In the NEJM paper, Smith's group reported they've managed to identify a fungus in less than a third of the specimens they've tested.

Suspicion rested on either the steroid or something in the clinic environment, Smith said. The steroid manufacturing company said Sept. 25 that it had received no reports of adverse events but agreed the next day to recall the product.

On Sept. 27, the focus of suspicion was narrowed further, when a report from North Carolina implicated the steroid in another case, the researchers reported.

By that time, Smith said, the CDC and state and local health departments were alerting physicians and beginning to contact people who had been exposed to the drug.

That quick action probably resulted in treatment for many people whose mild to moderate symptoms "ordinarily would not have prompted urgent medical evaluation," the researchers commented.

Smith and colleagues cautioned that, in many cases, they did not have data on which patients received injections from specific lots of the steroid, making it difficult to enumerate the exact numbers exposed.

The analysis was supported by the CDC.

Park is an employee of the agency. Other authors are employees of the CDC or of health departments involved in the outbreak.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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